In the field of cosmetics and dermatology, a wide variety of measures have been proposed and attempted to alleviate or treat injuries caused by the effects of the external environment and aging including the exposure of the skin to sunlight. For example, examples of skin changes accompanying aging primarily include the formation of wrinkles, and hardening or decreased resiliency.
Primary interest is being directed at decreased function of collagen fibers and elastic fibers composed of collagen, elastin and glucosaminoglycans in the skin dermis as the cause of such changes. In the past, the use of hydroxycarboxylic acids (e.g., Japanese Patent No. 2533339), and the use of lysophospholipids (e.g., Japanese Unexamined Patent Publication No. 8-67621) or that described in the Journal of the Japan Society of Fats and Oils, Vol. 46, No. 9 (1997), pp. 13-19 have been proposed as means for preventing or repairing such changes.
In the former publication, keratin and wrinkles have been suggested as being able to be eradicated by preventing decreases in collagen fibers. On the other hand, in the latter publication, lysophospholipids are suggested to demonstrate whitening effects by accelerating the production ability of glycosaminoglycans (and more specifically, hyaluronic acid) in human fibroblasts.
The most powerful effect of the above external environment on skin aging is produced by ultraviolet rays present in sunlight, and these ultraviolet rays have clearly been established to be a factor that promotes aging. Ultraviolet rays are known to induce skin changes referred to as photoaging that is characterized by deep wrinkles (Scharffetter-Kochanek, Advances in Pharmacology, 1997, 58, 639-655). Ultraviolet rays have a diverse range of effects on the skin, including damage to genetic DNA, induced production of active oxygen, and more recently, induced production of matrix-metalloproteinases (Fisher, et al., Nature, 1996, 379, 335-339).
Due to the multifunctional nature of ultraviolet rays, the mechanism by which this photoaging induced by ultraviolet rays occurs has not been adequately elucidated. Deep wrinkles corresponding to human photoaged skin have been clearly shown to form on the skin on the backs of hairless mice following continuous irradiation of ultraviolet rays at an energy level not enough to cause erythema. Substances having an effect on wrinkles have also been evaluated using this mouse model (Moloney, et al., Photochem. Photobiol. 1992, 56, 495-504). However, the wrinkle formation mechanism has still not been adequately elucidated and its elucidation is awaited.
On the other hand, Koivukangas, et al. reported in 1994 that levels of gelatinase, an enzyme that decomposes the basement membrane, becomes elevated in skin irradiated with ultraviolet rays (Acta Derm. Venereol. 1994, 74, 279-282). In addition, it has also been reported that the basement membrane exhibits structural changes at sites of the skin exposed to sunlight, and that reduplication is observed particularly frequently (Lavker, J. Invest. Dermal. 1979, 73, 59-66). This suggests the possibility that ultraviolet rays contained in sunlight have an effect on basement membrane structure by increasing the amount of basement membrane decomposing enzymes produced in the skin.
However, there is no specific means known for promoting the formation of skin basement membrane structure.
Artificial skin is important as an alternative to natural skin that has been damaged by some cause, or as an experimental material for testing the action and pharmacological effects of pharmaceuticals and cosmetics on the skin. In either of these applications, artificial skin is desired that has a structure that imitates the structure of natural skin as closely as possible.
Natural skin is roughly composed of the epidermis, dermis and basement membrane present between them. One example of a known production method of artificial skin that imitates natural skin involves the formation of an epidermal layer by culturing normal human epidermal keratinocytes on contracted type I collagen gel having a structure that resembles the dermis and contains human fibroblasts. In this method, however, there was the problem of inadequate formation of a basement membrane between the collagen gel imitating the dermis and the epidermal layer imitating the epidermis.